Paternal bisphenol a diet changes prefrontal cortex proteome and provokes behavioral dysfunction in male offspring

Chemosphere. 2017 Oct:184:720-729. doi: 10.1016/j.chemosphere.2017.06.050. Epub 2017 Jun 14.


Relatively little attention has been given paternal effects on next generation. Given that Bisphenol A (BPA), a ubiquitous compound in maternal diet, may disrupt brain development and behavior, we hypothesized that paternal BPA diet (PBD) could affect offspring development. Prefrontal cortex (PFC), a vital brain region, is involved in emotion and social behavior. To test whether PBD could alter developing PFC, we carried out a proteomics approach for PFC in male juvenile offspring that responded to PBD (50 mg BPA/kg diet). We found that PBD altered the expressions of binding immunoglobulin protein (BIP), CCAAT/-enhancer-binding protein homologous protein (CHOP) and B-cell lymphoma-2 (BCL-2), which could reflect endoplasmic reticulum (ER) stress. In addition, downregulation of myelinogenesis genes and myelin basic protein (MBP) could provoke myelin deficiency. Furthermore, PBD significantly increased anxiety-like behavior and impaired social behavior in male offspring. Taken together, these results revealed the alterations of ER stress and myelin destruction related molecules induced by PBD might be a potential mechanism for the behavior deficits in their male offspring. These findings remind us of the importance of paternal effects in the further environmental exposure research.

Keywords: Anxiety-like behavior; Immunoglobulin protein; Myelin basic protein; Paternal BPA diet; Social behavior.

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Behavior / drug effects*
  • Benzhydryl Compounds / metabolism
  • Benzhydryl Compounds / toxicity*
  • Diet / statistics & numerical data
  • Environmental Pollutants / toxicity*
  • Female
  • Male
  • Phenols / metabolism
  • Phenols / toxicity*
  • Prefrontal Cortex / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Proteome / metabolism*
  • Social Behavior


  • Benzhydryl Compounds
  • Environmental Pollutants
  • Phenols
  • Proteome
  • bisphenol A